Circulating Stromal Cell-Derived Factor 1α Levels in Heart Failure: A Matter of Proper Sampling

BackgroundThe chemokine Stromal cell-derived factor 1α (SDF1α, CXCL12) is currently under investigation as a biomarker for various cardiac diseases. The correct interpretation of SDF1α levels is complicated by the occurrence of truncated forms that possess an altered biological activity.MethodologyWe studied the immunoreactivities of SDF1α forms and evaluated the effect of adding a DPP4 inhibitor in sampling tubes on measured SDF1α levels. Using optimized sampling, we measured DPP4 activity and SDF1α levels in patients with varying degrees of heart failure.ResultsThe immunoreactivities of SDF1α and its degradation products were determined with three immunoassays. A one hour incubation of SDF1α with DPP4 at 37°C resulted in 2/3 loss of immunoreactivity in each of the assays. Incubation with serum gave a similar result. Using appropriate sampling, SDF1α levels were found to be significantly higher in those heart failure patients with a severe loss of left ventricular function. DPP4 activity in serum was not altered in the heart failure population. However, the DPP4 activity was found to be significantly decreased in patients with high SDF1α levelsConclusionsWe propose that all samples for SDF1α analysis should be collected in the presence of at least a DPP4 inhibitor. In doing so, we found higher SDF1α levels in subgroups of patients with heart failure. Our work supports the need for further research on the clinical relevance of SDF1α levels in cardiac disease.背景 目前，趋化因子基质细胞衍生因子1α（stromal cell-derived factor 1α, SDF1α, CXCL12）正作为多种心脏疾病的生物标志物被研究。但由于存在生物学活性发生改变的截短形式，准确解读SDF1α水平的过程变得复杂。 研究方法 我们探究了SDF1α各形式的免疫反应性，并评估了在采样管中添加二肽基肽酶4（Dipeptidyl peptidase 4, DPP4）抑制剂对检测所得SDF1α水平的影响。通过优化采样流程，我们对不同程度心力衰竭患者的DPP4活性与SDF1α水平进行了检测。 研究结果 我们采用三种免疫测定法，测定了SDF1α及其降解产物的免疫反应性。将SDF1α与DPP4在37℃下孵育1小时后，三种免疫测定法的免疫反应性均降低了2/3。与血清孵育也得到了相似的结果。采用恰当的采样方式后，我们发现左心室功能严重受损的心力衰竭患者的SDF1α水平显著升高。心力衰竭人群的血清DPP4活性未发生明显变化，但在SDF1α水平较高的患者中，其血清DPP4活性显著降低。 研究结论 我们建议，所有用于SDF1α分析的样本均应在至少含有DPP4抑制剂的条件下采集。通过该采样方式，我们在心力衰竭患者的亚群中检测到了更高水平的SDF1α。本研究支持需进一步探究心脏疾病中SDF1α水平的临床相关性。